Could a Genetic Test Predict the Risk for Suicide?

Why It Matters

About 39,000 people kill themselves in the U.S. each year. It is the 10th most common cause of death.

No one could have predicted that Oscar-winning comedian Robin Williams would kill himself.

Or could they?

When someone commits suicide, the reaction is often the same. It’s disbelief, mixed with a recognition that the signs were all there. Depression. Maybe talk of ending one’s life.

Now, by studying people who think about committing suicide, as well as brains of people who actually did, two groups of genome researchers in the U.S. and Europe are claiming they can use DNA tests to actually predict who will attempt suicide.

While claims for a suicide test remain preliminary, and controversial, a “suicide gene” is not as fanciful as it sounds. The chance that a person takes his or her own life is in fact heritable, and many scientific teams are now involved in broad expeditions across the human genome to locate suicide’s biological causes.

Based on such gene research, one startup company, Sundance Diagnostics, based in Boulder, Colorado, says it will begin offering a suicide risk test to doctors next month, but only in connection with patients taking antidepressant drugs like Prozac and Zoloft.

The Sundance test rests on research findings reported by the Max Planck Institute of Psychiatry in 2012. The German researchers, based in Munich, scanned the genes of 898 people taking antidepressants and identified 79 genetic markers they claimed together had a 91 percent probability of correctly predicting “suicidal ideation,” or imagining the act of suicide.

It’s well known that after going on antidepressants, some people do begin thinking about killing themselves. The risk is large enough that a decade ago the U.S. Food and Drug Administration slapped a warnings on antidepressant pills, saying they “increased the risk … of suicidal thinking and behavior” in children and young adults.

“The number of completed suicides is not large, but none of us want our loved one to be at risk. You wouldn’t play roulette if it was your child,” says Sundance CEO Kim Bechthold, who licensed the test idea from Max Planck. She says the DNA tests will be carried out on a saliva sample.

For now, however, experts say there are good reasons to view any suicide test with skepticism. Genome studies often turn up apparent connections that later are found not to mean much. Dozens of genes have been linked to suicide, but none in a truly definitive fashion.

“I don’t think there are any credible genomic tests for suicide risk or prevention,” says Muin J. Khoury, head of the Office of Public Health Genomics at the U.S. Centers for Disease Control and Prevention. According to the CDC, suicide is the 10th most common cause of death in the U.S., accounting for 39,518 deaths in 2011.

What is certain, says the CDC’s Khoury, is that suicide runs in families. On its list of suicide risk factors, the CDC lists family history first, followed by mistreatment of children, prior suicide attempts, and depression.

That family connection is what makes scientists certain that genes are involved. In 2013, for instance, Danish researchers looked at 221 adopted children who later in life committed suicide. They found that their biological siblings, raised in different households, were five times as likely to also commit suicide as other people. Identical twins are also more likely to both kill themselves than are two non-identical twins.

Altogether, epidemiologists believe that 30 percent to 55 percent of the risk that someone takes their own life is inherited, and the risk isn’t linked to any specific mental illness, like depression or schizophrenia.

That means suicide probably has its own unique genetic causes, says Stella Dracheva, a pathologist who studies the brains of suicide victims at the Icahn School of Medicine at Mount Sinai in New York. “Suicide is a very complex condition, but there is a lot of evidence that it has a biological base,” she says. “There is something different in people who commit suicide.”

In her view, that means it’s worth searching for suicide genes and that a DNA test is also theoretically plausible. She says a test would be particularly useful among veterans or other groups at unusually high risk of harming themselves.

A person’s life history still has more to do with whether it ends in suicide than genes do. Virginia Willour, a geneticist at the University of Iowa who studies suicidal thinking among bipolar patients, says environmental factors are especially important in preventing suicide. Getting medical treatment, an involved family, and religious beliefs all cut the chance of suicide dramatically.

Willour’s grandfather was bipolar and killed himself. “I chose to research suicidal behavior because I knew the impact. His suicide was a constant reminder and presence in my childhood,” she says.

The pain and disbelief surrounding suicide only raises the stakes for scientists claiming they can predict it. The latest report of a possible suicide test came in July from Johns Hopkins University, in Baltimore, where geneticists published a report saying that the presence of alterations to a single gene could predict who will attempt suicide with 80 percent accuracy.

That research, carried out by Zachary Kaminsky, an assistant professor of psychiatry at Johns Hopkins, began on a collection of a small number of brains of suicide victims held by the National Institutes of Health. Instead of looking just at DNA, they studied patterns of methylation, a type of chemical block on genes that can lower their activity. They found that one gene, SKA2, seemed to be blocked often in the suicide brains. They later found the same gene block was common when they tested the blood of a larger number of people having suicidal thoughts.

“We seem to be able to predict suicidal behavior and attempts, based on seeing these epigenetic changes in the blood,” says Kaminsky. “The caveat is that we have small sample sizes.”

Kaminsky says that following the report, his e-mail inbox was immediately flooded by people wanting the test. “They wanted to know, if my dad died from suicide, is my son at risk?” he says. They didn’t understand that the type of DNA change he identified probably isn’t the inherited kind, but instead may be the result of stress or some other environmental factor.

Kaminsky’s publication has drawn some criticism from scientists who say his conclusions were based on thin evidence. They say more data is needed. “It’s a striking finding, but as always, when you look at complex genetics, you need replication. Time will tell if it [stands up],” says Willour.

The bigger problem, says Dracheva, is that there are simply not enough brains of suicide victims to study. Unlike studies of diabetes or schizophrenia, where scientists can call on thousands or tens of thousands of patients, suicide studies remain small, and their findings much more tentative.

It’s because they don’t have DNA from enough people who committed suicide that researchers, including those at Hopkins and Max Planck, have had to try connecting the dots between DNA and whether or not people have suicidal thoughts. Yet there’s no straight line between the contemplation of suicide and actually doing it.